Compositions and methods for treating cancer
Patent Number: US9512138
Executive Summary:
General Description:
Lung cancer is the leading cause of cancer death. The poor prognosis for advanced non-small lung cell cancer (NSCLC) is caused by the onset of chemotherapy resistance. Conventional anti-cancer drugs could lead to the emergence and propagation of cancer stem cells (CSC) which are responsible to tumor maintenance and development of drug-resistance. Treatments with parthenolide (PTL), a compound derived from a plant known as feverfew, reverse chemotherapy resistance by killing CSC through inhibition of NF-kB and restoring cell death pathways. Bioavailability of PTL and feverfew extracts is very little. The invention claims the development of derivatives of PTL that have improved water solubility and antitumor activities. These compounds are able to inhibit NSCLC cell proliferation and the activation of the NF-kB pathway. This invention provides a new method for treatment of NSCLC and potentially other solid tumors though NF-kB inhibition and activation of cell death pathways.
Weaknesses:
Patent Status:
Publications:
Development of a new approach to kill non-small cell lung cancer cells with resistance to standard chemotherapy using parthenolide analogues. Diana C. Márquez-Garbán, Gang Deng, Hsiao-Wang Chen, Hermes J. Garbán, Michael E. Jung and Richard J. Pietras
Cancer Res 2012;72(8 Suppl):Abstract nr 3491. doi:1538-7445.AM2012-3491
Inventor Bio: Richard J. Pietras
https://ccim.med.ucla.edu/?page_id=218
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Active (Granted)
- Patent Link: https://patents.google.com/patent/US9512138/
- Research Institute: University of California, Los Angeles
- Disease Focus: Lung cancer, breast cancer
- Basis of Invention Synthesis of derivatives of Parthenolide (PTL), a naturally-occurring compound, with improved water solubility and anticancer activity
- How it works: Similar to PTL, these compounds inhibit NF-kB activation, thus restoring cell death pathways and overcoming chemotherapy-acquired drug resistance in solid tumors, such as lung (NSCLC) and breast (ER-positive and HER2-overexpressing) cancers
- Lead Challenge Inventor: Richard J. Pietras
- Inventors: Richard J. Pietras, Michael E. Jung, Diana C. Márquez-Garbán, Gang Deng
- Development Stage: Pre-clinical (only in vitro data)
- Novelty:
- Improved water solubility and anticancer activities of PTL derivatives
- Improved water solubility and anticancer activities of PTL derivatives
- Clinical Applications:
- Targeted therapy to treat cisplatin-resistant NSCLC, hormone-resistant ER-positive breast cancers and HER2-overexpressing breast cancers resistant to Herceptin
- Targeted therapy to treat cisplatin-resistant NSCLC, hormone-resistant ER-positive breast cancers and HER2-overexpressing breast cancers resistant to Herceptin
General Description:
Lung cancer is the leading cause of cancer death. The poor prognosis for advanced non-small lung cell cancer (NSCLC) is caused by the onset of chemotherapy resistance. Conventional anti-cancer drugs could lead to the emergence and propagation of cancer stem cells (CSC) which are responsible to tumor maintenance and development of drug-resistance. Treatments with parthenolide (PTL), a compound derived from a plant known as feverfew, reverse chemotherapy resistance by killing CSC through inhibition of NF-kB and restoring cell death pathways. Bioavailability of PTL and feverfew extracts is very little. The invention claims the development of derivatives of PTL that have improved water solubility and antitumor activities. These compounds are able to inhibit NSCLC cell proliferation and the activation of the NF-kB pathway. This invention provides a new method for treatment of NSCLC and potentially other solid tumors though NF-kB inhibition and activation of cell death pathways.
Weaknesses:
- Toxicity, efficacy and mechanism of action need to be further investigated
Patent Status:
- Priority date: 2012-04-02
- Filing date: 2016-01-07
- Publication date: 2016-12-06
- Grant date: 2016-12-06
Publications:
Development of a new approach to kill non-small cell lung cancer cells with resistance to standard chemotherapy using parthenolide analogues. Diana C. Márquez-Garbán, Gang Deng, Hsiao-Wang Chen, Hermes J. Garbán, Michael E. Jung and Richard J. Pietras
Cancer Res 2012;72(8 Suppl):Abstract nr 3491. doi:1538-7445.AM2012-3491
Inventor Bio: Richard J. Pietras
https://ccim.med.ucla.edu/?page_id=218